WASHINGTON--Two novel weight loss drugs led to significant
reductions in overweight and obese adults, based on the findings from
two phase III, placebo-controlled trials presented at the annual meeting
of the Obesity Society.

The drugs are not yet approved by the U.S. Food and Drug
Administration. If they are approved, they will provide additional
options for treating obesity.

In one study, Dr. Caroline Apovian of Boston University Medical
Center presented results of the Con-trave Obesity Research II (COR-II)
study, a phase III, double-blind trial of 1,496 adults with an average
age of 44 years and an average body mass index of 36 kg/[m.sup.2]. The
study involved Orexigen Therapeutics Inc.'s combination naltrexone SR/bupropion SR combination therapy (Contrave).

Participants were randomized to a single daily oral dose of the
combination drug NB32 (32 mg naltrexone/360 mg bupropion) or a placebo.

After 28 weeks, 56% of the treatment group participants achieved at
least a 5% weight loss--the study's primary outcome
measure--compared with 18% of the placebo group. A 10% weight loss was
achieved by 27% of the treatment group and 7% of the placebo group; a
15% loss was achieved by 10% and 2% of these groups. Baseline
demographics were similar between the treatment and placebo groups.

After 28 weeks, participants were re-randomized to a combination
drug including 48 mg naltrexone and 360 mg bupropion (NB48). "This
was a chance to see if there was a higher dose needed," she said,
but at 56 weeks, there was no significant change in weight loss with
NB48, compared with NB32.

Patients in the treatment group reported significant decreases in
food cravings compared with baseline, Dr. Apovian said. Approximately
half of the patients in the drug and placebo groups discontinued the
study, but discontinuation rates due to adverse events were low. Nausea,
the most common adverse event, was mild or moderate in most cases,
"and occurred mostly in the first 4 weeks."

The combination drug seemed to be well tolerated, and the safety
profile was consistent with previous data on the two drugs when used
separately, she added.

Orexigen intends to submit the drug for FDA approval in the first
half of 2010, according to a company statement.

Dr. Lee Kaplan of Harvard Medical School, Boston, presented results
of a study of lorcaserin, a selective 5-hydroxytryptamine 2C receptor
agonist designed to promote weight loss without the cardiovascular side
effects associated with nonspecific 5-HT agonists.

The randomized, double-blind, placebo-controlled phase III study
enrolled 4,008 patients, aged 18-65 years, for 52 weeks. The study
involved patients with a BMI of 27-45 kg/[m.sup.2] with and without at
least one comorbid condition. The average age was 44 years, the average
BMI was 36 kg/[m.sup.2], and 80% were female. Baseline demographics were
similar between the treatment and placebo groups.

Overall, the intent-to-treat analysis showed that a 5% weight loss
was achieved by 47% of participants who took 10 mg lorcaserin twice
daily, by 40% of those who took 10 mg lorcaserin once daily, and by 25%
of those who took a placebo, said Dr. Kaplan, who is also director of
the Massachusetts General Hospital weight center in Boston. Patients in
the twice-daily, once-daily, and placebo groups who completed the study
according to the protocol lost an average of 7.7 kg, 6.5 kg, and 3.9 kg,
respectively.

The most common adverse events were headache, fatigue, dizziness,
and nausea, each of which occurred in less than 5% of patients. Patients
with FDA-defined valvulopathy were included in the study, and the
lorcaserin was not associated with increased valvulopathy during the
study, Dr. Kaplan added. Lorcaserin has not yet been FDA approved.

Disclosures: Dr. Apovian is on the advisory board of Orexigen and
has received financial support from other pharmaceuticaf companies,
including Eli Lilly & Co. and Amgen. Dr. Kaplan said he has received
financial support from lorcaserin's manufacturer, Arena
Pharmaceuticals, among other pharmaceutical companies.

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